Osteoporosis is a disease where bone matrix becomes pathologically lean, and reduces bone mineral density and bone strength, which may consequently increase a risk of broken bones (DJ L. Clinical guide for management of osteoporosis, The Korean Journal of Internal Medicine 1999; 57(4):801-4).
Although bone is made of hard tissues, it is also active and constantly changing throughout our lives. With naked eyes, bone is classified into external cortical bone (compact bone) and internal trabecular bone (cancellous bone), where cortical bone has a physical strength to protect and support the body and trabecular bone is to absorb shocks or maintains calcium changes consistently. Physiologically, bone is also a place where bone remodeling is taking place continuously in order to replace bone matrix to new bone tissues (i.e. bone turnover), which balances it out between bone resorption and bone formation (Jerome C P Hormonal therapies and osteoporosis ILAR J. 2004; 45 (2): . . . 170-8). Thus, the bone mineral density and strength remain steadily in a healthy skeleton because of the bone remodeling that equalizes between bone resorption and bone formation. However, bone remodeling imbalances occur in an osteoporosis-induced bone because of greater bone resorption over bone formation, which leads to decrease in weight and bone mass. Then histologic bone atrophy may occur and skeletal physical strength may also be weakened, which can increase the incidence of fracture (Belchetz P E. Hormonal treatment of postmenopausal women. N Engl J Med. 1994 Apr. 14; 330 (15): 1062-71).
Osteoporosis is a typical metabolic bone disorder, which is caused by the significant quantitative reduction of bone mass, compared to those observed in people of the same age and gender. Riggs and Melton, et al. classified osteoporosis into Type 1 osteoporosis (postmenopausal osteoporosis) or primary osteoporosis, and Type II osteoporosis (senile osteoporosis) or secondary osteoporosis.
Postmenopausal osteoporosis, the Type 1 primary osteoporosis is the most representative metabolic bone disease, and clinically causes more problems such as bone pain, bone fracture and deformity for the elderly (Lee W S PHBD. Prevalence of Osteoporosis in Korean Women. The Journal of Korean Society of Menopause. 2003; 9 (4): 339-46).
Osteoporosis therapeutic agents used these days include bisphosphonate agents (alendronate, etidronate, ibandronate, risedronate, zoledronic, etc.), hormones (raloxifene), vitamin D agents, calcitonin agents, and calcium agents, etc. Recently, parathyroid hormone agents such as Forteo™ are commercially available that are effective on bone formation. However, hormone agents need to be taken throughout the life and there are side effects such as breast cancer, uterine cancer, gallstones and thrombosis when administered a long term. Vitamin D agents are expensive and not reliably effective, and calcitonin agents are expensive and difficult to administer. Although calcium agents have fewer side effects, their functions are limited to preventing rather than treating. Recently commercialized parathyroid hormone agent Forteo™ is effective on bone formation, which compensates shortcomings of existing drugs that only suppress bone resorption. However, Forteo™ needs to be injected every day for a long time and has a side effect of excessive bone formation. It is also too expensive to be widely used.
Thus, the most commonly prescribed osteoporosis medication is from a series of the bisphosphonates. These medications have demonstrated effectiveness in increasing bone mineral density and preventing fracture by intensively suppressing bone resorption. They are also advantageous since they may be administered orally and are cost effective, and thus have been widely used in clinical practices for osteoporosis and other calcium metabolic disorders. However, a bisphosphonate agent has a very complicated intake instruction since it has a low absorption rate and induces esophagitis. Hence it is advised to be taken with plenty of water before breakfast and observe at least 30 minutes of fast, and one shouldn't lie for a certain period of time after the intake. Also, there has been a report the bisphosphonate agent increases the risk of hypocalcaemia.
Recent studies suggest the bisphosphonate agent has clinical problems such as a decreased bone turnover rate resulted from excessive bone resorption inhibition and bone formation inhibition by affecting bone generation rate, gastrointestinal disorder, and jaw bone necrosis. According to a recent research, it may increase the risk of fractures when taken for an extended period of time (Andrew S Neviaser etc., Journal of Orthopaedic Trauma, 2008, 22 (5), 346˜350).
Therefore, there has been a need to develop a new substance that has superior efficacy without the above side effects.
Schisandra fructus (Schisandra chinensis) is characterized as having five distinguishable tastes: sweetness, sourness, bitterness, saltiness, and spiciness, and mainly grows around Mt. Taebaek. Kadsura (Kadsura japonica) is known to grow in the southern island province, and Black-berry magnolia vine (Schisandra repanda) in Jeju Island. Schisandra chinensis is known to grow wild in Korea, Japan, Sakhalin Island, and China. Schisandra fructus contains ingredients such as schizandrin, gomisin, citral, malic acid, and citric acid that strengthen heart, lower blood pressure and increase the immunity, and it has been used as a cardio-tonic. It is also a known as antitussive and expectorant that effectively relieves coughing and thirst, and enhances the lung function.
Eucommia tree (Eucommiae cortex OLIV) is a deciduous tall tree originated from China and belongs to Eucommiaceae. Its dry rhizodermis () is called Eucommiae cortex (), and is known to have hypotensive action and diuretic action. Gutta-percha, alkaloid, pectin, jinbang, and resins are known to be included therein (Unabridged Dictionary of Native Herbal Medicines, Bo-seop, Jeong et al., Younglim Publishing Co., p 605-606, 1998), as well as aucubin and geniposide (the promoting effects of geniposidic acid and aucubin in Eucommiae cortex Oliver leaves on collagen synthesis./Li Y, Sato T, Metori K, Koike K, Che Q M, Takahashi S/Biological & Pharmaceutical Bulletin [1998, 21 (12): 1306-1310]).
Lycii fructus is a fruits from Lycium chinense Miller or Lycium barbarum Linne, and contains various functional substances such as carotenoids, choline, meliscic acid, zeaxanthin, physalin (dipalmity-zeaxanthin), betaine, β-sitosterol, vitamin B1, rutin and unsaturated fatty acids, etc. Not only that, there are various studies and reports to support that it has anti-oxidant, anti-aging, anti-bacterial and anti-diabetic effects; improves liver function; lowers blood pressure; enhance immune system; lower blood cholesterol; prevent cardiovascular-related disease; and has an anti-cancer effect.
Although there have been disclosures on various extracts comprising the combined extracts comprising Schisandra fructus, Eucommiae cortex or Lycii fructus, there has never been a disclosure relating to combined extracts comprising all of Schisandra fructus, Eucommiae cortex and Lycii fructus. Furthermore, there is no prior art suggesting synergy effect thereof.